Biocompatibility and Efficacy of a Linearly Cross-Linked Sodium Hyaluronic Acid Hydrogel as a Retinal Patch in Rhegmatogenous Retinal Detachment Repairment

Abstract

To prevent the migration of retinal pigment epithelium (RPE) cells into the vitreous cavity through retinal breaks after the pars plana vitrectomy for the repair of rhegmatogenous retinal detachment (RRD), sealing retinal breaks with an appropriate material appears to be a logical approach. According to a review of ocular experiments or clinical trials, the procedure for covering retinal breaks with adhesives is complex. A commercially available cross-linked sodium hyaluronic acid (HA) hydrogel (Healaflow®) with the injectable property was demonstrated to be a perfect retinal patch in RRD clinical trials by our team. Based on the properties of Healaflow®, a linearly cross-linked sodium HA hydrogel (HA-engineered hydrogel) (Qisheng Biological Preparation Co. Ltd. Shanghai, China) with the injectable property was designed, whose cross-linker and cross-linking method was improved. The purpose of this study is to report the characteristics of an HA-engineered hydrogel using Healaflow® as a reference, and the biocompatibility and efficacy of the HA-engineered hydrogel as a retinal patch in the rabbit RRD model. The HA-engineered hydrogel exhibited similar dynamic viscosity and cohesiveness and G′ compared with Healaflow®. The G′ of the HA-engineered hydrogel varied from 80 to 160 Pa at 2% strain under 25°C, and remained constantly higher than G″ over the range of frequency from 0.1 to 10 Hz. In the animal experiment, clinical examinations, electroretinograms, and histology suggested no adverse effects of the HA-engineered hydrogel on retinal function and morphology, confirming its favorable biocompatibility. Simultaneously, our results demonstrated the efficacy of the HA-engineered hydrogel as a retinal patch in the RRD model of rabbit eyes, which can aid in the complete reattachment of the retina without the need for expansile gas or silicone oil endotamponade. The HA-engineered hydrogel could play the role of an ophthalmologic sealant due to its high viscosity and cohesiveness. This pilot study of a small series of RRD models with a short-term follow-up provides preliminary evidence to support the favorable biocompatibility and efficacy of the HA-engineered hydrogel as a promising retinal patch for sealing retinal breaks in retinal detachment repair. More cases and longer follow-up studies are needed to assess its safety and long-term effects.

The effect of hyaluronic acid and iodine complex gel compared to Vaseline on deep second‐degree burn wound in rats

“…A study by De Bouelle et al on the efficacy and safety of topical iodine products in wound care highlighted potential cytotoxic effects of iodine on fibroblasts and keratinocytes, which can delay wound healing, especially at high concentrations 15 . On the other hand, the study by Zheng et al on the biocompatibility and efficacy of a linearly cross‐linked sodium hyaluronic acid hydrogel found it to be well tolerated with no adverse effects on retinal function and morphology, suggesting its potential as a promising retinal patch for sealing retinal breaks 16 . Iodine, particularly in the form of povidone‐iodine, has been a staple in wound care for its antimicrobial properties for many years.…”

“… 15 On the other hand, the study by Zheng et al on the biocompatibility and efficacy of a linearly cross‐linked sodium hyaluronic acid hydrogel found it to be well tolerated with no adverse effects on retinal function and morphology, suggesting its potential as a promising retinal patch for sealing retinal breaks. 16 Iodine, particularly in the form of povidone‐iodine, has been a staple in wound care for its antimicrobial properties for many years. Its efficacy against a broad spectrum of pathogens, including antibiotic‐resistant strains, is well documented.…”

Innovative Strategies for Drug Delivery to the Ocular Posterior Segment

“…Hydrogels have been developed to deliver proteins, peptides, and antibodies, as the formation of the hydrogel can occur at ambient temperature conditions. These components are currently used in clinical research utilizing soft contact lenses and foldable intraocular lenses to deliver drugs to the anterior segment and to the posterior segment of the eye and have been considered in the treatment of diabetic retinopathy, age-related macular degeneration, or rhegmatogenous retinal detachment [ 177 , 191 , 192 , 193 ].…”

Advances in biomaterials as a retinal patch for the repair of rhegmatogenous retinal detachment

“…This causes the development of proliferative fibrocellular membranes with the ability to contract, which facilitates the progression of tractional retinal detachment ( Figure 2 ). ( Pastor et al, 2016 ; Zheng et al, 2022 ).…”

“…The fundamental role of long-lasting vitreous substitutes is to keep the neurosensory retina attached to the RPE and prevent liquid flow between the vitreous cavity and the subretinal space until the chorioretinal adhesion becomes firm enough to seal the retinal breaks. ( Feltgen and Walter, 2014 ; Zheng et al, 2022 ) However, the tamponade property of long-lasting vitreous substitutes requires a long-term postoperative face-down position, given that their gravity is lower than that of the aqueous humor. Moreover, the visual quality is poor during this period because the refractive index of vitreous substitutes is lower or higher (1.00 in expansile gas and 1.40 in silocone oil) than in the natural human vitreous (1.33).…”